Peripheral circulation miRNA expression of pediatric brain tumors and its relation to tumor miRNA expression levels.

Abstract

Micro RNAs (miRNAs) in peripheral biofluids (e.g., blood, saliva, urine) have been investigated as potential sources of diagnostic and prognostic information for a variety of tumor types, including pediatric brain tumors. While significant predictive associations have been identified between unique serum miRNA concentrations and some pediatric brain tumors, it is unclear whether serum miRNA abnormalities in pediatric brain tumor patients are representative of miRNA alterations in the tumor tissue compartment or whether they represent host tissue reactions to the presence of a brain tumor. The authors sought to identify whether serum miRNA changes in pediatric brain tumor patient sera could be explained by miRNA alterations within their tumors. Matched serum and tissue samples were taken from a cohort of pediatric brain tumor patients (juvenile pilocytic astrocytoma [JPA] = 3, medulloblastoma = 4, ependymoma = 3), and unmatched control samples (n = 5) were acquired from control pediatric patients without oncological diagnoses. Extracted RNAs were tested within an array of 84 miRNAs previously noted to be relevant in a variety of brain tumors. miR-26a-5p correlated strongly in JPA patients within both the serum and tumor tissue samples (R2 = 0.951, p = 0.046), and serum levels were highly predictive of JPA (area under the curve = 0.751, p = 0.027). No other miRNAs that were significantly correlated between biological compartments were significantly associated with brain tumor type. In total, 15 of 84 tested miRNAs in JPA patients, 14 of 84 tested miRNAs in ependymoma patients, and 4 of 84 tested miRNAs in medulloblastoma patients were significantly, positively correlated between serum and tumor tissue compartments (R2 > 0.950, p < 0.05). The majority of miRNA changes in pediatric brain tumor patient sera that are significantly associated with the presence of a brain tumor do not correlate with brain tumor miRNA expression levels. This suggests that peripheral miRNA changes within pediatric brain tumor patients likely derive from tissues other than the tumors themselves.